ABSTRACT The overall objectives of the University of Chicago Medicine Comprehensive Cancer Center (UCCCC) Advanced Imaging (AI) Program are to improve cancer detection and treatment by applying functional and anatomic imaging to noninvasively study cancer initiation, progression, and metastasis. Underpinning this research is the Program?s unique expertise in quantitative image acquisition, analysis and reconstruction, and development of image-based biomarkers. Imaging plays a key role in the UCCCC's efforts to develop precision medicine through the use of non-invasive methods to assess individual risk, find early cancer, guide treatment delivery, assess therapeutic response, and evaluate and prevent adverse health outcomes - particularly for breast, prostate, and lung cancer (cancers with increased incidence and/or mortality in our catchment area). The AI Program is developing more robust predictive biomarkers, imaging strategies, and therapeutic approaches. Noninvasive anatomic, functional, and molecular imaging is used to guide therapy based on specific physiologic, anatomic, metabolic, and molecular characteristics of each tumor. In addition, the AI Program is developing and testing sophisticated image-guided therapies, such as intensity-modulated radiation therapy (IMRT) and MRI-guided high-intensity focused ultrasound (HIFU) that can deliver optimal treatments locally using minimally invasive approaches. The themes around which our research efforts are organized include: 1) Image-based screening; 2) Image-guided therapy; 3) Radiomics; and 4) Molecular imaging. To support and enhance applications of imaging to cancer, the Program continues to foster strong collaborations between imaging scientists, cancer biologists, and physician scientists to share expertise, determine the most relevant research questions, and identify new opportunities for use of imaging and image-guided therapy in both clinical and basic research arenas. UCCCC-supported joint meetings, an interdisciplinary Imaging Working Group, and targeted retreats/symposia facilitate these efforts. The result is a highly collaborative, productive, and well-integrated imaging program, as evidenced by the number of inter- and intraprogrammatic publications (25% and 28%, respectively, 239 publications, 2013-2016), inter-institutional publications (48.5%) and collaborative funding. The AI Program includes 19 members from Radiology and Radiation and Cellular Oncology across a wide range of disciplines, from imaging physics to radiation physics, and radiology to radiation oncology. Research includes studies of patients, volunteers, animal models, tissues, and materials, simulations, data-mining, and development of new devices ? all focused on cancer. Total support for the AI Program is $3.29 million (direct costs), and includes $1,710,047 from the NCI, $1,058,332 from other NIH Institutes, and $521,509 from other sources. Future plans include enhancing each of the four thematic areas, with an emphasis on leveraging the new Cyclotron Facility and expanding the radiochemistry program, as well as conducting clinical trials of screening and risk evaluation.